Magnetic resonance imaging (MRI) of metabolic markers offers a powerful method to screen and diagnose diseases as well as to gauge response to treatment. Yet at Boltzmann equilibrium, spin polarizations of conventional MR (on the order of ˜10−5-10−6) are too low, and the metabolites are often too dilute, to detect, quantify, or image such substances in vivo on a reasonable time-scale. However, spin order attained by ‘hyperpolarizing’ substances beyond Boltzmann levels can be high enough to overcome such otherwise-poor detection sensitivity. Because the high nuclear spin polarization is independent of magnetic field, strong magnetic fields are unnecessary for some applications, permitting low/zero-field MRS/MRI, and even remotely-detected MRS/MRI.
Known hyperpolarization techniques include dynamic nuclear polarization (DNP) and Optical Pumping; however, another route to address the NMR/MRI sensitivity problem is to use parahydrogen (pH2) as the hyperpolarization source, as is done in a family of techniques referred to collectively as Parahydrogen-Induced Polarization (PHIP). In traditional PHIP, molecular precursors with unsaturated chemical bonds are hydrogenated via molecular addition of pH2, thereby transferring the nuclear spin order to the molecular products. In a more recent variant, referred to as Signal Amplification by Reversible Exchange (SABRE), spin order may be transferred from pH2 to target molecules during the lifetime of transient molecular complexes without permanent chemical change.
Catalysis plays a role in both PHIP approaches, as they each generally require an organometallic catalyst to facilitate the underlying chemical reactions; this typically takes place under conditions of homogeneous catalysis—a process wherein the catalyst molecules are dissolved within the same phase as the reagents. Thus, the wider biological application of PHIP for production of highly polarized liquids is constrained by the difficulty of separating the potentially toxic and expensive catalyst substances from the created hyperpolarized (HP) agents. Furthermore, the chemistry of both liquid phase SABRE and aqueous PHIP first requires catalyst activation, often resulting in the release of chelating substances (e.g. octadiene, norbornadiene, or derivatives) into the liquid phase. Thus, there exists a need for new catalysts and methods in order to broaden the applicability of SABRE.